Osteoporosis is the most common form of metabolic bone disease. It is a chronic disease characterized by low bone mineral density (BMD), which results in a high incidence of bone fractures, especially of the hip. The mechanism by which bone is lost in osteoporotics is believed to be the imbalance in the process by which the skeleton renews itself. In a healthy adult, there is a balance between the rates of bone formation and bone resorption.
Post-menopausal women are particularly at risk to imbalances in the rates of bone formation and resorption and likely to develop idiopathic osteoporosis (“post-menopausal osteoporosis”). Post-menopausal osteoporosis occurs in about 50% of women over 50 years of age and those who suffer from hip fracture become dependent on others for daily activities (Ray et al., “Medical Expenditures for the Treatment of Osteoporotic Fractures in the United States in 1995: Report from the National Osteoporosis Foundation,” J. Bone Miner. Res. 12:24-35 (1997); Ross P. D., “Osteoporosis. Frequency, Consequences, and Risk Factors,” Arch. Intern. Med. 156:1399-411 (1996)). In the United States alone, the cost—both direct (i.e. hospitalization, surgery, doctor's visits) and indirect (i.e. loss time from work)—from factures exceeds $7 billion annually.
Several risk factors have been identified in relation to osteoporosis: genetic predisposition, sedentary lifestyle, low dietary intake of calcium and vitamin D, physical activity, petite stature and small bone fracture, long-term use of steroids or heparin, cigarette smoking, and declining levels of estrogen after menopause (Society NAM, “Management of Osteoporosis in Post-Menopausal Women: 2006 Position Statement of the North American Menopause Society,” Menopause 13:340-367 (2006)). Estrogen deficiency is considered one of the most important risk factors (Choo et al., “Osteoporosis in Relation to Menopause,” Ann. Acad. Med. Singapore 31:30-6 (2002); Kanis J. A., “Estrogens, the Menopause, and Osteoporosis,” Bone 19 (5 Suppl.):185S-190S (1996)), because bone loss accelerates 2-3 years after menopause at a rate of 1-1.5% annually (Recker et al., “Characterization of Peri-menopausal Bone Loss: a Prospective Study,” J. Bone Miner. Res. 15:1965-73 (2000)). Hormone replacement therapy (HRT) is partially effective in slowing down bone loss in post-menopausal women (Ravn et al., “Alendronate and Estrogen-progestin in the Long-term Prevention of Bone Loss: Four-year Results from the Early Post-menopausal Intervention Cohort Study. A Randomized, Controlled Trial,” Ann. Intern. Med. 131:935-42 (1999)). The partial alleviation of HRT also suggests that factors other than estrogen may play an important role in post-menopausal osteoporosis (Society NAM, “Management of Osteoporosis in Post-menopausal Women: 2006 Position Statement of The North American Menopause Society,” Menopause 13:340-367 (2006)).
A number of treatments have been suggested for osteoporosis. Most agents used to treat osteoporosis, such as hormones, parathyroids, bisphosphonates, are not very effective and these treatments cause significant side effects, e.g. osteonecrosis caused by bisphosphonates (Grewal et al. “Bisphosphonate-associated Osteonecrosis: A Clinician's Reference to Patient Management,” Todays FDA 20:38-41, 43-6 (2008)).
Thus, there is a need in the art for a safe and effective way of treating, preventing, or reducing the risk of bone deterioration or osteoporosis, particularly in peri- or post-menopausal women.
The present invention is directed to overcoming these and other deficiencies in the art.